Present investigation was conducted to examine the chemical renal carcinogenesis using N-ethyl-N-hydroxyethylnitrosamine (EHEN) as a initiator and beta-cyclodextrin (beta-C) as a promoter in dogs.In one of preliminary studies, we examined nephrotoxicity of subcutaneous administration of beta-C in dogs. Because signs of nephrotoxicity represented were noted in dogs after beta-C treatment, as has been reported in rats, it seems likely that dogs also can serve as a model of nephrosis. If this model is to be applied to the study of renal carcinogenesis, this study suggested the optimum dosing regimen for beta-C to be 7-day 0.45g/kg treatment.In another preliminary study, we examined various parameters, which are clinically used as tumor markers of renal cell carcinoma, in renal tumor-bearing rats induced by EHEN. The results from this experiment suggested that erythropoietin (EP) was specially elevated in rats with renal tumor.In the present experiment, seven female Beagle dogs, weighing 8
… More.1-10.5kg (mean : 9.2kg) were used. The animals were divided into five groups : Group 1 (2 dogs treated with 300mg of EHEN and with subsequent beta-C), Group 2 (2 dogs treated with 150mg of EHEN and with subsequent beta-C), Group 3 (1 dog treated with 300mg of EHEN alone), Group 4 (1 dog treated with 150mg of EHEN alone) and Group 5 (1 dog treated with beta-C alone). Duration of oral administration of EHEN was 14 days. All animals were followed with ultrasonography (US) of the kidneys and blood sampling for various parameters. Those examinations were performed every 3 months from the beginning of the experiment. On 18 months (79 weeks), US indicated no tumor formation in the dog kidneys in all groups. In addition, no significant elevations were noted in any parameters including EP.Further observations of those animals with US and blood sampling should be continued.第3群:EHEN 300mgを14日間連続経口投与のみ行う群(1頭)。第4群:EHEN 150mgを14日間連続経口投与のみ行う群(1頭)。第5群:βーC 0.45g/kgを7日間連続皮下投与のみ行う群(1頭)。前年度より本実験を継続中で、経時的に超音波検査にて腎の形態を観察しているが、現時点まで腫瘍の発生は認められなかった。また、ヒト腎細胞癌の腫瘍マ-カ-も経時的に観察しているが、とくに著明な変化はみられていない。なお、EHEN誘発腎腫瘍ラットでは、エリスロポエチン(Ep)が腫瘍マ-カ-となりうる結果を得たが、本実験ではEpもとくに上昇がみられなかった。今後とも継続して、経過観察を行う予定である。 Less